PROJECT SUMMARY No pharmacologic treatments have been identified to prevent or treat Alzheimer?s disease. To date, non- pharmacological approaches that target modifiable risks through lifestyle interventions provide the most promising evidence for disease delay. The impact of highly prevalent and chronic cardiometabolic conditions in older Americans places an important spotlight on the long prodromal period that precedes the development of Alzheimer?s and other dementias ? for prevention. The U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER) uses a multi-domain intervention approach that has proven successful for cardiovascular disease and diabetes prevention, and for cognitive function in a Finnish cohort of older adults. U.S. POINTER launches in Fall 2018 to investigate whether random assignment to one of two lifestyle interventions that differ in structure, intensity, and accountability influences cognitive trajectory over 2 years in 2000 cognitively normal older adults (age 60-79 yrs) who are at increased risk for cognitive decline, Alzheimer?s disease and other dementias. The ancillary study, POINTER-zzz, will add in-home objective sleep assessments for 700 parent trial participants to examine the effects of lifestyle modification and cardiovascular risk management on sleep disturbances that have been linked to cognitive decline and Alzheimer?s disease. In older adults, chronic sleep disturbances marked by sleep-disordered breathing and sleep fragmentation are associated with impaired hippocampal functioning, greater brain beta-amyloid burden, and increased risk for Alzheimer?s disease. These and other sleep abnormalities are also associated with reduced cardiovascular and cerebrovascular health. Although there is some evidence to suggest that diet, exercise, and cardiometabolic risk reduction can improve sleep and that improved sleep benefits cognitive function in older adults, these effects have not been confirmed in a large-scale rigorous clinical trial with comprehensive and objective measures of sleep. POINTER-zzz provides an unprecedented opportunity to leverage extensive resources provided by a multi-site randomized controlled prevention trial in a well-characterized cohort of cognitively normal but Alzheimer-vulnerable adults to test the effects of a 2-year intensive lifestyle intervention on sleep-disordered breathing using oximetry and on sleep fragmentation using actigraphy. POINTER-zzz will also examine whether changes in sleep predict changes in global and domain-specific cognitive function and other parent trial outcomes. POINTER-zzz results may identify an effective strategy for improving sleep that could have important consequences for the prevention of Alzheimer?s disease and related dementias.